Co–Ferrocene MOF/Glucose Oxidase as Cascade Nanozyme for Effective Tumor Therapy

Abstract Chemodynamic therapy (CDT), enabling selective therapeutic effects and low side effect, attracts increasing attention in recent years. However, limited intracellular content of H2O2 and acid at the tumor site restrains the lasting Fenton reaction and thus the anticancer efficacy of CDT. Herein, a nanoscale Co–ferrocene metal–organic framework (Co‐Fc NMOF) with high Fenton activity is synthesized and combined with glucose oxidase (GOx) to construct a cascade enzymatic/Fenton catalytic platform (Co‐Fc@GOx) for enhanced tumor treatment. In this system, Co‐Fc NMOF not only acts as a versatile and effective delivery cargo of GOx molecules to modulate the reaction conditions, but also possesses excellent Fenton effect for the generation of highly toxic •OH. In the tumor microenvironment, GOx delivered by Co‐Fc NMOF catalyzes endogenous glucose to gluconic acid and H2O2. The intracellular acidity and the on‐site content of H2O2 are consequently promoted, which in turn favors the Fenton reaction of Co‐Fc NMOF and enhances the generation of reactive oxygen species (ROS). Both in vitro and in vivo results demonstrate that this cascade enzymatic/Fenton catalytic reaction triggered by Co‐Fc@GOx nanozyme enables remarkable anticancer properties.